We have used Southern blotting to characterize the restriction fragment length polymorphism of the human Ha-ras locus. Twenty-five allelic restriction fragments have thus far been detected. Of these, fifteen are rare, with individual allelic frequencies less than 0.005. All of the fifteen rare allelic fragments are detected only in cancer patient tumor or white blood cell DNA. Both leukemias and solid tumors demonstrate these rare alleles. Approximately 20% of cancer patients possess them. Therefore, the Ha-ras locus may prove useful in genetic risk assessment. We are currently conducting a population study to determine allelic frequencies by decade of life. In this manner, we hope to identify high risk Ha-ras alleles and to quantitate the relative degree of risk among such alleles. (X)